Linker Wang resin

Polystyrene resin with a hydroxymethylphenoxy linker (Wang resin)1 was originally developed for solid-phase peptide synthesis... 

Because no treatment with acid is required during peptide assembly, peptide synthesis with Fmoc amino acids can be conducted on acid-sensitive supports (e.g. Tenta-gel) and with acid-labile linkers. Wang resin is suitable for most purposes, but other supports, such as Sasrin or 2-chlorotrityl resin, can also be used. CPG, macroporous... 

Wang linker, mimic 297 Wang resin, phthalimide library synthesis 103... 

The investigation of minor groove-binding polyamides was greatly accelerated by the implementation of solid-phase synthesis [48]. Originally demonstrated on Boc-y9-Ala-PAM resin with Boc-protected monomers, it was also shown that Fmoc chemistry could be employed with suitably protected monomers and Fmoc-y9-Ala-Wang resin (Fig. 3.8) [49]. Recently, Pessi and coworkers used a sulfonamide-based safety-catch resin to prepare derivatives of hairpin polyamides [50]. Upon activation of the linker, resin-bound polyamides were readily cleaved with stoichiometric quantities of nucleophile to provide thioesters or peptide conjugates. 

A very similar approach to the same solid-phase supported dendrimers was reported by Portnoy and coworkers by means of iterative Mitsunobu/reduction steps starting with a Wang resin [56]. They used [Gl] (loading 0.62 mmol g ) to [G3] (loading 0.32 mmol g ) dendrimers for synthetic applications. The synthesis of a tripeptide was carried out without previous linker introduction to yield a dendri-... 

Tyr Ura UV Val Wang resin XAL linker Z 5-tyrosine uracil ultraviolet 5-valine cross-linked polystyrene with 4-benzyloxybenzyl alcohol linker Sieber linker, 3-alkoxy-9//-9-xanthenylamine Cbz, benzyloxycarbonyl... 

As illustrated by the examples in Table 3.9, resin-bound 4-alkoxybenzylamides often require higher concentrations of TFA and longer reaction times than carboxylic acids esterified to Wang resin. For this reason, the more acid-sensitive di- or (trialkoxy-benzyl)amines [208] are generally preferred as backbone amide linkers. The required resin-bound, secondary benzylamines can readily be prepared by reductive amination of resin-bound benzaldehydes (Section 10.1.4 and Figure 3.17 [209]) or by A-alkyla-tion of primary amines with resin-bound benzyl halides or sulfonates (Section 10.1.1.1). Sufficiently acidic amides can also be A-alkylated by resin-bound benzyl alcohols under Mitsunobu conditions (see, e.g., [210] attachment to Sasrin of Fmoc cycloserine, an O-alkyl hydroxamic acid). 

Examples of the preparation of oxazines and thiazines on insoluble supports are listed in Table 15.34. 3,l-Benzoxazin-4-ones can be prepared by intramolecular O-acy-lation of /V-aminocarbonyl anthranilic acids (Entry 1, Table 15.34). The resulting ben-zoxazinones are sufficiently stable towards acids to enable TFA-mediated cleavage from a Wang linker [410]. 1,3-Oxazines have also been obtained by acidolytic cleavage of functionalized 3-amino-l-propanols from Wang resin (Entry 4, Table 3.30). 

The first one (Scheme 55) uses the p-oxyphenylsulfonyl linker attached to the Wang resin by the Mitsunobu procedure [216, 217] whereas the second one (Scheme 56) utilizes alkylation of the lithium salt of a mesylate [218] with the terminal of the Merrifield resin [216, 219]. 

Abbreviations DBU, l,8-diazabicyclo[5.4.0]undec-7-ene DMF, A/fV-dimethylformamide MCPBA, 3-chloroperbenzoic acid NMP, A-methyl-2-pyrrolidinone Pol, undefined polymeric support PS, cross-linked polystyrene Wang resin, 1-2% cross-linked polystyrene with p-benzyloxybenzyl alcohol linker. 

The prototype of a functional group with an appropriate breakable bond is the Wang resin 3, which contains a 4-hydroxybenzyl alcohol linker moiety. The benzyl alcohol hydroxyl group can be functionalized using either electrophilic or nucleophilic substrates (Scheme 6.1.1) to give a benzylic linkage. It is very stable in many reactions, but can be cleaved by acids such as trifluoroacetic acid or HF. Acids, alcohols, esters, and amides can be obtained as products after cleavage. 

The halide linkers 1.8 (64), which can be prepared from Wang resin, have been used to support amines and to release sulfonamides using 95% TFA-DCM (R = H) or 5% TFA-DCM (R = OMe). 

In a related study, Lusinchi [11] reported the synthesis of a new soluble polymer containing a p-alkoxybenzyl alcohol linker, analogous to Wang resin. The polymer was utilized in intermolecular radical addition reactions. The polymer was synthesized by subjecting xanthate 65, formed in three steps from alcohol 63, to styrene polymerization in the presence of lauroyl peroxide... 

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